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A MASTERCLASS IN: VENOUS THROMBOEMBOLISM (VTE) Dr. Tom Heaps Consultant Acute Physician

A MASTERCLASS IN: VENOUS THROMBOEMBOLISM (VTE) Dr. Tom Heaps Consultant Acute Physician

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Page 1: A MASTERCLASS IN: VENOUS THROMBOEMBOLISM (VTE) Dr. Tom Heaps Consultant Acute Physician

A MASTERCLASS IN:VENOUS THROMBOEMBOLISM

(VTE)

Dr. Tom HeapsConsultant Acute Physician

Page 2: A MASTERCLASS IN: VENOUS THROMBOEMBOLISM (VTE) Dr. Tom Heaps Consultant Acute Physician

LEARNING OUTCOMES AND FORMAT

By the end of this session you should be familiar with the presentation, investigation and management of both routine and complex aspects of venous thromboembolic disease

Interactive case-based discussion format based on recent national clinical guidance and my own clinical experience and learning

Page 3: A MASTERCLASS IN: VENOUS THROMBOEMBOLISM (VTE) Dr. Tom Heaps Consultant Acute Physician

CASE 1: INVESTIGATION OF DVT

45-year-old male presents to AEC with acute left leg swelling

no significant PMH

FY1 clerks patient and asks you whether to take a d-dimer or not

HOW DO YOU RESPOND AND HOW SHOULD YOU PROCEED FROM HERE?

Page 4: A MASTERCLASS IN: VENOUS THROMBOEMBOLISM (VTE) Dr. Tom Heaps Consultant Acute Physician

CASE 1: INVESTIGATION OF DVT Assess clinical pre-test probability

Wells score

Low clinical probability or ‘DVT unlikely’ (modified Wells Score) Check d-dimer USS if d-dimer positive

Intermediate/High clinical probability or ‘DVT likely’ (modified Wells score) USS (do not check d-dimer)

Compression doppler USS Sensitivity 98.7% and specificity 100% for above-knee DVT Sensitivity 85.2% and specificity 98.2% for below-knee DVT

Page 5: A MASTERCLASS IN: VENOUS THROMBOEMBOLISM (VTE) Dr. Tom Heaps Consultant Acute Physician

CASE 1: INVESTIGATION OF DVT

WHAT ARE YOUR OPTIONS IF USS IS INCONCLUSIVE OR NEGATIVE WITH A HIGH PERSISTING CLINICAL SUSPICION FOR DVT?

administer LMWH for 1/52 and recall patient for repeat USS

CT or MR venogram

invasive venography

Page 6: A MASTERCLASS IN: VENOUS THROMBOEMBOLISM (VTE) Dr. Tom Heaps Consultant Acute Physician

CASE 2: INVESTIGATION OF PE

76-year-old female no previous Hx of VTE never smoked referred to ED with acute onset pleuritic chest pain CXR NAD heart rate 102/min, other observations NAD

IS HER CLINICAL PRESENTATION SUGGESTIVE OF PE?

HOW WOULD YOU PROCEED FROM HERE?

Page 7: A MASTERCLASS IN: VENOUS THROMBOEMBOLISM (VTE) Dr. Tom Heaps Consultant Acute Physician

CASE 2: PRESENTATIONS OF PE

1. pleuritic chest pain, tachycardia, haemoptysis +/- abnormal CXR

• peripheral PE

2. unexplained dyspnoea and/or hypoxaemia • moderate or chronic PE

3. acute cor pulmonale and syncope• massive PE with RV outflow obstruction

Page 8: A MASTERCLASS IN: VENOUS THROMBOEMBOLISM (VTE) Dr. Tom Heaps Consultant Acute Physician

CASE 2: CLINICAL FEATURES IN PE

CLINICAL FEATURES ALONE ARE UNRELIABLE (have a low threshold for suspicion);

Major risk factors for VTE absent in 40% Signs of coexistent DVT in ≤15% Triad of pleuritic pain, dyspnoea and haemoptysis <10% Normal A-a gradient in 6% No dyspnoea, tachypnoea, pleuritic pain or hypoxaemia in

3%

SUSPECT DIAGNOSIS OF PE; COPD patients with acute dyspnoea and no/minimal signs of

infection Any unwell patient with cancer Younger patients with unusually severe ‘pneumonia’ Recurrent unexplained syncope Sudden deterioration as an inpatient or post-surgery

Page 9: A MASTERCLASS IN: VENOUS THROMBOEMBOLISM (VTE) Dr. Tom Heaps Consultant Acute Physician

CASE 2: INVESTIGATION OF PE

ASSESS THE CLINICAL PRE-TEST PROBABILITY AS FOR DVT Wells score Geneva score BTS guideline Pulmonary embolism rule-out criteria (PERC)

age <50 years pulse <100bpm SpO2 >94% on air no unilateral leg swelling IF ALL SATISFIED, RISK OF

PE <2% no haemoptysis no recent trauma or surgery no prior PE or DVT no hormone use

1. patient has clinical features compatible with PE – breathlessness and/or tachypnoea with or without pleuritic chest pain and/or haemoptysis plus;

2. absence of another reasonable clinical explanation and/or;

3. presence of a major risk factor for VTE

Where 2. and 3. are both true the probability is high; if only one is true the probability is intermediate; and if neither is true the probability is low

Page 10: A MASTERCLASS IN: VENOUS THROMBOEMBOLISM (VTE) Dr. Tom Heaps Consultant Acute Physician

CASE 2: INVESTIGATION OF PE

Low or intermediate pre-test probability or ‘PE unlikely’ Check d-dimer if hospital uses SimpliRED assay only check d-

dimer if low probability if d-dimer positive proceed to imaging (V/Q or

CTPA)

High pre-test probability or ‘PE likely’ (modified Wells) DO NOT check d-dimer Proceed straight to definitive imaging

Page 11: A MASTERCLASS IN: VENOUS THROMBOEMBOLISM (VTE) Dr. Tom Heaps Consultant Acute Physician

D-DIMERS Only measure AFTER assessment of pre-test clinical probability: LOW OR

INTERMEDIATE

High sensitivity (>95%) ELISA-based d-dimer assays (Vidas, MDA) low specificity (40% in outpatients)

negative in <30% of outpatients

Moderate sensitivity (80-94%) d-dimer assays (SimpliRED) more specific (70%)

can only be used to exclude VTE in patients with low clinical pre-test probability

Llimited value in patients with HIGH clinical pre-test probability of PE 50% will have a positive result due to the presence of PE

negative predictive value greatly reduced by high prevalence of disease i.e. if d-dimer <0.5μg/ml;

post-test probability for PE <2% if low pre-test probability but 19-28% if high pre-test probability

 specificity reduced by age, pregnancy, cancer, inflammatory conditions, trauma and surgery

using age-adjusted upper limits of normal (age/10) for patients aged >50 may increase specificity without affecting sensitivity

Page 12: A MASTERCLASS IN: VENOUS THROMBOEMBOLISM (VTE) Dr. Tom Heaps Consultant Acute Physician

CASE 2: INVESTIGATION OF PE

76-year-old female no previous Hx of VTE never smoked referred to ED with acute onset pleuritic chest pain CXR NAD heart rate 102/min, other observations NAD

patient has a Wells score of 1.0 = low clinical probability

d-dimer 498ng/ml (>243ng/ml considered positive)

WHAT INVESTIGATION SHOULD YOU REQUEST NEXT?

Page 13: A MASTERCLASS IN: VENOUS THROMBOEMBOLISM (VTE) Dr. Tom Heaps Consultant Acute Physician

DIAGNOSIS OF PE – V/Q SCANS

less radiation than CTPA

overall sensitivity low at 55%

normal perfusion scan in only 25% of people without a PE only useful if young, non-smoker, no respiratory disease

consequently up to 70% of scans non–diagnostic CTPA required after V/Q

do not show alternative pathologies

Page 14: A MASTERCLASS IN: VENOUS THROMBOEMBOLISM (VTE) Dr. Tom Heaps Consultant Acute Physician

LIKELIHOOD OF PE BASED ON POSITIVE V/Q SCAN (PIOPED)

Scan Result

Clinical Probability of PE

High Intermediate Low

High Probability 95 86 56

Intermediate Probability 66 28 15

Low Probability 40 15 4

Normal 0 2 2

Page 15: A MASTERCLASS IN: VENOUS THROMBOEMBOLISM (VTE) Dr. Tom Heaps Consultant Acute Physician

DIAGNOSIS OF PE - CTPA Higher radiation dose (women of child-bearing age)

Overall sensitivity of 86% and specificity of 96% in PIOPED II

Positive predictive value varies with extent of PE; 97% for main/lobar c/w 25% subsegmental clinical pre-test probability; 96% if high c/w 58% if low

Overall sensitivity increased to 90% with addition of lower limb CT venogram

Sensitivity probably higher with modern multi-detector CT scanners

May miss subsegmental clot mortality <1% if anticoagulation witheld 94% with subsegmental clot have evidence of more proximal PE

May assist in diagnosing alternative/coexisting pathologies (e.g. pneumonia, lung cancer) and provide information on thrombus burden and RV strain

Page 16: A MASTERCLASS IN: VENOUS THROMBOEMBOLISM (VTE) Dr. Tom Heaps Consultant Acute Physician

DIAGNOSIS OF PE – CXR

abnormal CXR in 84% in PIOPED e.g. atelectasis, pleural effusion

main role of CXR is to rule out alternative or coexisting pathology e.g.

pneumothorax assist in determining suitability for V/Q

Hampton’s Hump

Fleischner’s Sign

Westermark’s Sign

Page 17: A MASTERCLASS IN: VENOUS THROMBOEMBOLISM (VTE) Dr. Tom Heaps Consultant Acute Physician

DIAGNOSIS OF PE – OTHER TESTS

ECG abnormal in 70% Sinus tachycardia most common Atrial arrhythmias T wave inversion V1-3 and inferior leads ST depression or elevation S1Q3T3 RBBB

ECHO abnormal in up to 40% Useful in emergency situation, pulmonary HTN, RV

strain/dilatation

Troponin and BNP Elevated levels in significant PE correlate with prognosis

Page 18: A MASTERCLASS IN: VENOUS THROMBOEMBOLISM (VTE) Dr. Tom Heaps Consultant Acute Physician

CASE 3: MANAGEMENT OF VTE

58-year-old male Acutely breathless 10d post-right total knee replacement Multiple segmental PE confirmed on CTPA No significant PMHx and no previous VTE Haemodynamically stable with normal ECG and hs-TnI

WHAT TREATMENTS ARE YOU GOING TO PRESCRIBE?

HOW MIGHT YOUR PRESCRIPTION CHANGE IF THE PATIENT WAS MUSLIM?

FOR HOW LONG ARE YOU GOING TO RECOMMEND ANTICOAGULATION?

Page 19: A MASTERCLASS IN: VENOUS THROMBOEMBOLISM (VTE) Dr. Tom Heaps Consultant Acute Physician

CASE 3: MANAGEMENT OF VTE - WARFARIN

Start LMWH immediately once diagnosis confirmed (before scan if high CPTP or anticipated delay in imaging >4h) SC Enoxaparin (Clexane®) 1.5mg/kg OD (1mg/kg OD if GFR <30) continue for 48h once INR >2 and for a minimum of 5d in total SC Fondaparinux 5-10mg OD is alternative if objection to porcine

products

Start warfarin after diagnosis confirmed by imaging aiming for INR 2.0-3.0

1. Isolated calf vein thrombosis with transient (reversible) risk factor ≥6weeks

2. Proximal DVT or PE with transient (reversible) risk factor ≥3months

3. Isolated calf vein thrombosis which is unprovoked (idiopathic) ≥3months

4. Proximal DVT or PE which is unprovoked (idiopathic) ≥6months*

5. Recurrent (second or subsequent) DVT or PE indefinite

*consider longer-term or indefinite anticoagulation in all patients

Page 20: A MASTERCLASS IN: VENOUS THROMBOEMBOLISM (VTE) Dr. Tom Heaps Consultant Acute Physician

CASE 3: MANAGEMENT OF VTE patient states that he is needle-phobic

will not agree to regular blood tests for INR monitoring

asks about ‘some new tablets for treating blood clots’ that he has read about on the internet

WHAT NOVEL ANTICOAGULANTS ARE AVAILABLE FOR THE TREATMENT OF VTE?

WHAT ARE THE PROS AND CONS OF THESE AGENTS?

Page 21: A MASTERCLASS IN: VENOUS THROMBOEMBOLISM (VTE) Dr. Tom Heaps Consultant Acute Physician

CASE 3: MANAGEMENT OF VTE – NOVEL ANTICOAGULANTS

PO rivaroxiban (Xarelto®) is a factor Xa inhibitor 15mg BD for 21d then 20mg OD (no need for LMWH) Currently licensed for acute Rx of DVT/PE and prevention of

recurrent DVT/PE, need GFR >30mL/min

PO dabigatran (Pradaxa®) is a direct thrombin inhibitor 110-150mg OD AFTER 5d initial treatment with LMWH Currently only licensed for prophylaxis of VTE after hip or

knee surgery in adults

PO apixaban and edoxaban are alternative factor Xa inhibitors

Page 22: A MASTERCLASS IN: VENOUS THROMBOEMBOLISM (VTE) Dr. Tom Heaps Consultant Acute Physician

CASE 3: MANAGEMENT OF VTE – NOVEL ANTICOAGULANTS

PROSNon-inferiority to warfarin (VTE recurrence rates and all-cause mortality) demonstrated in recent meta-analysesNon-significant trends towards lower rates of major haemorrhage overall (less ICH, more UGIB)No requirement for regular monitoring/blood tests/dose changes

CONSExpensive £75.60 for 60 tablets of dabigatran and £112.00 for 60 tablets of rivaroxaban (c/w £1.84 for 60 tablets of warfarin)Higher incidence of SE esp. GI (nausea, dyspepsia, diarrhoea)Long-term effects/efficacy unknown; higher rates of ACS with dabigatranNo reliable method for rapid reversal of anticoagulation (discontinue drug, supportive care, activated charcoal, PCC, rFVIIa, FEIBA)

Page 23: A MASTERCLASS IN: VENOUS THROMBOEMBOLISM (VTE) Dr. Tom Heaps Consultant Acute Physician

CASE 4: THROMBOLYSIS FOR PE

75-year-old female admitted acutely breathless Previous PE post-THR aged 62 Looks unwell RR 31, SpO2 90% on air, HR 104, BP 130/67 CTPA large volume thrombus in main pulmonary arteries

bilaterally with some RV dilatation Signs of RH strain on ECG and hs-TnI 48

SHOULD SHE RECEIVE THROMBOLYSIS?

Page 24: A MASTERCLASS IN: VENOUS THROMBOEMBOLISM (VTE) Dr. Tom Heaps Consultant Acute Physician

CASE 4: THROMBOLYSIS FOR PE Alteplase 10mg stat then 90mg over 2h then IV UFH (no loading dose) once

APTT <2x ULN

Massive PE with hypotension (sBP <90mmHg or fall in sBP ≥40mmHg for ≥15 minutes once other causes excluded)

accelerates clot lysis and has short-term haemodynamic benefits no meta-analysis conclusively showing reduction in mortality or recurrent PE consistent non-significant trends towards improved long-term outcomes recommended by NICE if not high risk for bleeding

Submassive PE (normal BP but evidence of RV dysfunction on ECHO, RV dilatation on CTPA, RV strain on ECG and/or raised troponin)

reduces risk of in-hospital death and clinical/haemodynamic deterioration requiring escalation (PEITHO)

no effect on risk of recurrent PE or overall mortality Excess risk of major haemorrhage 9% vs 6% (may be confined to certain

subgroups) Lower rates of pulmonary hypertension with similar bleeding risk using low-dose

alteplase 10mg bolus followed by 40mg infusion (MOPPET) not recommended by NICE consider on case-by-case basis with second (senior) opinion

Page 25: A MASTERCLASS IN: VENOUS THROMBOEMBOLISM (VTE) Dr. Tom Heaps Consultant Acute Physician

CASE 5

39-year-old male with no PMHx Referred from ED with acutely swollen left arm Decorating house 2 days prior to onset

WHAT IS THE DIAGNOSIS?

HOW WILL YOU CONFIRM THIS?

HOW WILL YOU TREAT?

Page 26: A MASTERCLASS IN: VENOUS THROMBOEMBOLISM (VTE) Dr. Tom Heaps Consultant Acute Physician

CASE 5: UPPER EXTREMITY DVT

Primary (20%)venous thoracic outlet syndrome (1st rib, clavicle, subclavius, anterior scalene band)effort-related thrombosis (Paget-Schroetter syndrome)acquired/hereditary thrombophilia

Secondary (80%) catheter associated (indwelling central venous catheter, PPM, defibrillator)cancer-relatedsurgery/trauma to arm/shoulderpregnancy/use of OCP

compression US, CTA/MRA, conventional venogram, CXR/CT thorax

anticoagulate for >3m with warfarin

catheter-directed thrombolysis for clinically massive UEDVT

SVC filter or surgical thrombectomy if treatment failure or CI to anticoagulation

Page 27: A MASTERCLASS IN: VENOUS THROMBOEMBOLISM (VTE) Dr. Tom Heaps Consultant Acute Physician

CASE 6

68-year-old female PMHx varicose veins Referred to Acute Medical Clinic ‘swollen painful R leg ?DVT’ OEx prominent distal long saphenous vein on R, associated

erythema, hardness and tenderness, minimal R leg swelling

WHAT IS THE DIAGNOSIS?

DOES SHE REQUIRE AN ULTRASOUND?

HOW SHOULD SHE BE TREATED?

Page 28: A MASTERCLASS IN: VENOUS THROMBOEMBOLISM (VTE) Dr. Tom Heaps Consultant Acute Physician

CASE 6: SUPERFICIAL THROMBOPHLEBITIS up to 20% with proximal superficial thrombophlebitis have an

underlying DVT at presentation

risk of progression to DVT in a further 3-4%

compression USS if proximal superficial thrombophlebitis

topical NSAIDs or hirudoid for symptomatic relief

TEDS

prophylactic dose LMWH for 30d (or fondaparinux 2.5mg for 45d) for proximal superficial thrombophlebitis

treatment dose LMWH for 6-12w if proximal thrombophlebitis approaching or at saphenofemoral junction

oral NSAIDs for 10d if distal superficial thrombophlebitis (or proximal and anticoagulation CI (less effective than LMWH)

Page 29: A MASTERCLASS IN: VENOUS THROMBOEMBOLISM (VTE) Dr. Tom Heaps Consultant Acute Physician

CASE 7

27-year-old male Current IVDU and alcohol abuse Presents to ED with extensive L leg swelling Immediate therapeutic dose of LMWH given Doppler USS confirms extensive L ileofemoral DVT

WHAT IS THE MANAGEMENT?

Page 30: A MASTERCLASS IN: VENOUS THROMBOEMBOLISM (VTE) Dr. Tom Heaps Consultant Acute Physician

CASE 7: VTE AND IVDU

Limited evidence available Difficult venous access for INR checks Poor compliance with warfarin and attendance at

anticoagulation clinics due to chaotic lifestyle Co-existing alcohol misuse common LMWH for ≥6w (ideally 6m) is treatment of choice (consider

rivaroxaban)

Shortly after returning from scan patient becomes pale and clammy, hypotensive, significant haematemesis witnessed

HOW SHOULD HE BE MANAGED NOW?

Page 31: A MASTERCLASS IN: VENOUS THROMBOEMBOLISM (VTE) Dr. Tom Heaps Consultant Acute Physician

CASE 7: IVC FILTERS

most IVC filters are retrievable and licensed for short-term use only; anticoagulation contraindicated interruption of anticoagulation required e.g. for surgery or

delivery within 4w of extensive proximal DVT recurrent PE from continuing DVT despite adequate anticoagulation pulmonary vascular bed compromised such that another embolic

event would be poorly tolerated (e.g. massive PE, severe pulmonary hypertension due to chronic thromboembolic disease, severe COPD)

effective short-term in preventing PE do not reduce mortality or recurrent symptomatic PE in the long-

term increase incidence of recurrent DVT

Page 32: A MASTERCLASS IN: VENOUS THROMBOEMBOLISM (VTE) Dr. Tom Heaps Consultant Acute Physician

CASE 8

31-year-old female Confirmed R ileofemoral DVT History of DVT in mother at age 52 No other significant RF for VTE

HOW LONG SHOULD SHE BE ANTICOAGULATED FOR?

SHOULD SHE BE TESTED FOR HERITABLE THROMBOPHILIA?

Page 33: A MASTERCLASS IN: VENOUS THROMBOEMBOLISM (VTE) Dr. Tom Heaps Consultant Acute Physician

CASE 8: DURATION OF ANTICOAGULATION FOLLOWING FIRST UNPROVOKED (IDIOPATHIC) PROXIMAL DVT/PE

risk of recurrent VTE approximately double that if thrombosis was distal or provoked

10% risk of recurrence at 1y and 30% by 5y following discontinuation of warfarin

indefinite warfarin therapy reduces risk by 90% to ≤1% per year risk of recurrence and case fatality rate with recurrence decrease with time

from initial event (highest in first 6m) whereas risk of major bleeding increases with age

factors increasing risk of recurrence idiopathic/unprovoked VTE presentation with PE or proximal DVT (rather than distal DVT) male sex (?influence of oestrogens) duration of anticoagulation <3m ongoing risk factors (e.g. obesity, immobility, malignancy, IBD, thrombophilia) residual venous obstruction/thrombus on ultrasound persistently elevated d-dimer/thrombin levels after period of anticoagulation

consider long-term or indefinite anticoagulation on an individual patient basis

take into account patient values/preferences and annual risk of bleeding with warfarin

potential role for newer oral anticoagulants?

Page 34: A MASTERCLASS IN: VENOUS THROMBOEMBOLISM (VTE) Dr. Tom Heaps Consultant Acute Physician

CASE 8: THROMBOPHILIA SCREENING Thrombophilia screening tests for commonest heritable

thrombophilias; Activated Protein C resistance Factor V Leiden (if APCR positive) Protein C and Protein S deficiency Prothrombin gene mutation Antithrombin III deficiency Lupus anticoagulant and Anticardiolipin antibodies

Thrombophilia screening is CI if obvious provoking factor for VTE active/acute thrombosis on anticoagulation therapy pregnant taking OCP or HRT

Page 35: A MASTERCLASS IN: VENOUS THROMBOEMBOLISM (VTE) Dr. Tom Heaps Consultant Acute Physician

CASE 8: THROMBOPHILIA SCREENING no clear international consensus on who should be tested

NICE Clinical Guideline CG144 (June 2012)

do not test patients who have decided to continue indefinite anticoagulation

consider testing for antiphospholipid antibodies only in patients with unprovoked DVT/PE if they are planning to stop anticoagulation

consider full testing in patients with unprovoked DVT/PE and a 1⁰ relative who has had DVT or PE if they are planning to stop anticoagulation

do not test patients who have had provoked DVT or PE

do not routinely test 1⁰ relatives of people with VTE and thrombophilia

other potential indications for thrombophilia testing

young patients with atypical VTE (cerebral venous sinus, axillary, mesenteric)

young patients with unexplained arterial thromboses

patients with a history of recurrent miscarriage, pre-eclampsia, placental abruption, IUGR or unexplained stillbirth

Page 36: A MASTERCLASS IN: VENOUS THROMBOEMBOLISM (VTE) Dr. Tom Heaps Consultant Acute Physician

CASE 8: THROMBOPHILIA SCREENING - CAVEATS

negative test does not exclude a heritable thrombophilia

positive test after unprovoked VTE rarely affects management no overall difference in rates of VTE recurrence biggest risk for recurrence is prior episode of VTE itself

no evidence that testing improves outcome for asymptomatic family

significant costs involved and potential for creating unnecessary anxiety

may influence decision to continue anticoagulation long-term

Page 37: A MASTERCLASS IN: VENOUS THROMBOEMBOLISM (VTE) Dr. Tom Heaps Consultant Acute Physician

CASE 9

65-year-old male diagnosed with PE 4 weeks after elective THR no significant PMHx observations all stable no RV strain on CTPA or ECG

CAN HE BE SAFELY MANAGED AS AN OUTPATIENT?

Page 38: A MASTERCLASS IN: VENOUS THROMBOEMBOLISM (VTE) Dr. Tom Heaps Consultant Acute Physician

CASE 9: OUTPATIENT MANAGEMENT OF PE no national clinical guidance

locally agreed protocols

use of scoring systems Pulmonary Embolism

Severity Index (PESI) Geneva Risk Score (GRS)

Prognostic Variable Points

agemale sexcancerheart failurechronic lung diseasepulse ≥110 per minutesystolic BP <100mmHgrespiratory rate ≥30 per minutetemperature <36ºCaltered mental status arterial oxygen saturation <90%

+ age+10+30+10+10+20+30+20+20+60+20

Class Risk Total Points 30-Day Mortality (%)

I very low <65 0-1.6

II low 66-85 1.7-3.5

III intermediate 86-105 3.2-7.1

IV high 106-125 4.0-11.4

V very high >125 10.0-24.5

Page 39: A MASTERCLASS IN: VENOUS THROMBOEMBOLISM (VTE) Dr. Tom Heaps Consultant Acute Physician

CASE 10

64-year-old female admitted with cellulitis L leg 3rd admission this year L leg swollen and painful

following extensive proximal DVT 3 years ago (6/12 warfarin)

WHAT IS THE DIAGNOSIS?

HOW COULD THIS HAVE BEEN PREVENTED?

Page 40: A MASTERCLASS IN: VENOUS THROMBOEMBOLISM (VTE) Dr. Tom Heaps Consultant Acute Physician

CASE 10: POST-THROMBOTIC SYNDROME (PTS)

persistent venous obstruction, valvular incompetence and reflux

affects 43% of patients with DVT by 2y (30% mild, 10% moderate, 3% severe)

higher incidence in those with proximal (ileofemoral) DVT (only 20% recanalization)

extensive clot, persisting obstruction, previous ipsilateral DVT, high BMI, older age, female

painful heavy oedematous leg, parasthesiae, cramps, pruritus, varicosities, hyperpigmentation, ulceration and recurrent infections (significant impact on QOL)

immediate mobilization and grade II-III (20-40mmHg) below-knee graduated compression stocking (NOT TEDS) on affected side for ≥2y after proximal DVT

reduces incidence of PTS by up to 50%

consider catheter-directed thrombolysis within 14d of symptomatic ileofemoral DVT in patients with good functional status, life expectancy >1y and low risk of bleeding (NICE CG144)

reduced risk of PTS from 78% to 27% and improved QOL in one study

Page 41: A MASTERCLASS IN: VENOUS THROMBOEMBOLISM (VTE) Dr. Tom Heaps Consultant Acute Physician

CASE 11

72-year-old male admitted with ‘unprovoked’ proximal DVT R leg ex-smoker nil specific on systems review physical examination unremarkable

HOW AGGRESSIVELY SHOULD HE BE SCREENED FOR OCCULT MALIGNANCY?

Page 42: A MASTERCLASS IN: VENOUS THROMBOEMBOLISM (VTE) Dr. Tom Heaps Consultant Acute Physician

CASE 11: SCREENING FOR MALIGNANCY

3-fold increased risk of occult cancer (incidence 20% by 2y) in those with ‘idiopathic’ VTE

no high quality evidence for cost effectiveness or improved survival with aggressive diagnostic testing for occult malignancy

diagnosis of cancer would result in change to pharmacological treatment and duration of anticoagulation

evaluation recommended by NICE CG144 for patients with unprovoked VTE focused history thorough physical examination (including DRE) CXR urinalysis FBC, LFTs, calcium (not PSA routinely) if all above are normal consider CT abdomen/pelvis (plus mammogram in women) if age

>40

more aggressive screening may be warranted in those with recurrent ‘idiopathic’ VTE

}basic screening detects cancer in ~10% of patients with idiopathic/unprovoked VTE

Page 43: A MASTERCLASS IN: VENOUS THROMBOEMBOLISM (VTE) Dr. Tom Heaps Consultant Acute Physician

CASE 11 CONTINUED

CXR reveals a large soft tissue mass at the right lung base CT and biopsy confirms metastatic small cell lung cancer commenced on long-term LMWH for his DVT and scheduled

for chemoradiotherapy as an outpatient readmitted 10d after discharge with acutely ischaemic L

leg platelet count 63 (189 on discharge)

WHAT IS THE DIAGNOSIS?

HOW IS THIS CONFIRMED AND TREATED?

Page 44: A MASTERCLASS IN: VENOUS THROMBOEMBOLISM (VTE) Dr. Tom Heaps Consultant Acute Physician

CASE 11: HEPARIN-INDUCED THROMBOCYTOPENIA (HIT)

antibody mediated thrombocytopenia (fall in platelet count >30% from baseline) in the presence of new venous or arterial thrombosis occurring 5-10d after starting LMWH

estimate pre-test probability of HIT using the ‘four Ts’

send blood (2x red top and 2x pink top) to haematology lab for transfer to Bristol if high (6-8) or intermediate (4-5) pre-test probability score

liaise with haematology regarding management

discontinuation of LMWH

use IV lepirudin infusion until platelet count >100 and warfarin or alternative anticoagulant (e.g. SC fondaparinux) can be started

Score 2 Score 1 Score 0

Thrombocytopenia (acute)

Platelet nadir 20-100

(or any platelet fall >50%)

Platelet nadir 10-19

(or any platelet fall 30–50%)

Platelet nadir <10

(or any platelet fall <30%)

Timing of onset of platelet fall (or other sequelae of HIT)

Days 5–10 >Day 10 or timing unclear

< Day 4

(no recent heparin)

Thrombosis or other sequelae

Proven new thrombosis; skin necrosis; or acute

systemic reaction after IV UFH

Progressive or recurrent thrombosis;

erythematous skin lesions; suspected

thrombosis (not proven)

None

OTher cause(s) of platelet fall

None evident Possible Definite

Page 45: A MASTERCLASS IN: VENOUS THROMBOEMBOLISM (VTE) Dr. Tom Heaps Consultant Acute Physician

CASE 12

24-year-old female 28 weeks pregnant (first pregnancy) pleuritic chest pain and dyspnoea ECG sinus tachycardia, S1Q3T3

respiratory alkalosis on ABG

HOW WOULD YOU INVESTIGATE FOR PE?

HOW WOULD YOU TREAT IF PE CONFIRMED?

Page 46: A MASTERCLASS IN: VENOUS THROMBOEMBOLISM (VTE) Dr. Tom Heaps Consultant Acute Physician

CASE 12: VTE AND PREGNANCY

VTE is a leading cause of preventable maternal death (2/100,000 pregnancies)

failure to take symptoms seriously and under-investigation are common

VTE is 6x more common in pregnancy than outwith pregnancy

risk maximal in late pregnancy/early puerperium (1st trimester - 3m postpartum)

up to 50% with VTE in pregnancy have heritable thrombophilia (esp. FVL)

other RF include previous VTE, obesity, dehydration, smoking, age >35, twins, multiparity, pre-eclampsia, ovarian hyperstimulation syndrome

85% of DVTs occur on left (55% outside of pregnancy)

72% of DVTs are ileofemoral/proximal (9% outside of pregnancy)

leg oedema and calf pain are common in normal pregnancy

long-term complications in young healthy women severe PTS (10%) and chronic pulmonary HTN (4%)

Page 47: A MASTERCLASS IN: VENOUS THROMBOEMBOLISM (VTE) Dr. Tom Heaps Consultant Acute Physician

CASE 12: VTE IN PREGNANCY – DIAGNOSIS

d-dimer positive in 80% by 2nd trimester and 100% by 3rd trimester

negative d-dimer should not be used to exclude VTE in pregnancy

sinus tachycardia, rightward axis and S1Q3T3 on ECG and respiratory alkalosis on ABG are NORMAL findings in pregnancy

CXR <0.01mGy to foetus = 9d background radiation (1.8mGy/y) or transatlantic flight

bilateral leg USS low yield in the absence of clinical DVT and 3% risk of false +ve

in pregnancy)

Page 48: A MASTERCLASS IN: VENOUS THROMBOEMBOLISM (VTE) Dr. Tom Heaps Consultant Acute Physician

CASE 12: VTE IN PREGNANCY – DIAGNOSIS

V/Q perfusion only 0.5mGy + ventilation (0.1mGy) if positive

inconclusive scans in only 20% (70% in general population)

CTPA 1/10 radiation of V/Q (0.05mGy) to foetus but 20x more to maternal breast

lifetime risk of breast cancer for females ~1/8

excess lifetime risk of breast cancer 1/3500 at age 40, 1/1200 at age 20

overall increased relative lifetime risk of breast cancer 1.004

risk may be reduced further by use of breast shields and modified protocols

CXR, V/Q, CTPA and conventional pulmonary angiography combined gives <9/12 background radiation to foetus

Page 49: A MASTERCLASS IN: VENOUS THROMBOEMBOLISM (VTE) Dr. Tom Heaps Consultant Acute Physician

CASE 12: VTE IN PREGNANCY - TREATMENT warfarin is teratogenic in (early) pregnancy (safe during breastfeeding)

LMWH is safe during pregnancy

different dosing e.g. enoxaparin 1mg/kg BD

check platelet count after 2 weeks of Rx (HIT)

anti-factor Xa monitoring needed only if ↓↓ or ↑↑ BMI or GFR <30ml/min

discontinue LMWH temporarily 24h prior to delivery; restart after 6-12h

continue anticoagulation for ≥6w after delivery and for ≥6m in total

switch to warfarin 1w after delivery

prophylactic LMWH antenatally in subsequent pregnancies

Page 50: A MASTERCLASS IN: VENOUS THROMBOEMBOLISM (VTE) Dr. Tom Heaps Consultant Acute Physician

CASE 13

36-year-old female 3m post-partum (C-section) uncomplicated pregnancy No history of VTE Left leg severely swollen/oedematous to groin, 1/52 Hx No cellulitis, lymphadenopathy or pelvic mass D-dimer 579ng/mL USS left leg no evidence of proximal DVT

WHAT NEXT?

Page 51: A MASTERCLASS IN: VENOUS THROMBOEMBOLISM (VTE) Dr. Tom Heaps Consultant Acute Physician

CASE 13 CONT.

Treated with LMWH for 1/52 Recalled for repeat USS L leg plus abdomen/pelvis USS NAD L leg more swollen with blue discolouration R leg also starting to swell CT venogram abdomen and pelvis L iliac vein thrombosis extending into IVC

Page 52: A MASTERCLASS IN: VENOUS THROMBOEMBOLISM (VTE) Dr. Tom Heaps Consultant Acute Physician

CASE 13: PELVIC DVT USS will miss isolated pelvic (iliac) DVT and IVC thrombosis

Risk factors for pelvic DVT Hormonal therapy Pregnancy Pelvic trauma or surgery (including C-section) IBD, diverticulitis Pelvic malignancy

High index of suspicion in patients with otherwise unexplained unilateral/bilateral leg swelling and risk factors for VTE if USS negative

Diagnosis with CTV or MRV

Page 53: A MASTERCLASS IN: VENOUS THROMBOEMBOLISM (VTE) Dr. Tom Heaps Consultant Acute Physician

CASE 14 42-year-old Chinese male Idiopathic proximal L leg DVT age 34

warfarin for 6/12 Recurrent unprovoked proximal L leg DVT 3/12

ago indefinite warfarin therapy

Now presents with acutely increasing pain and swelling affecting left leg ‘? recurrent DVT on warfarin’

WHAT DO YOU NEED TO KNOW?

Page 54: A MASTERCLASS IN: VENOUS THROMBOEMBOLISM (VTE) Dr. Tom Heaps Consultant Acute Physician

CASE 14: ‘RECURRENT’ VTE

1. Has his INR consistently been in target range?

2. Are his symptoms due to residual/chronic thrombus and/or PTS or a ‘new’ episode of VTE? often impossible to distinguish on USS low recanalization rates (<20%) in proximal DVT USS still abnormal in 50% after 1y of Rx for

proximal DVT persistent thrombus/obstruction and/or elevated d-

dimer may influence decision to continue warfarin

Page 55: A MASTERCLASS IN: VENOUS THROMBOEMBOLISM (VTE) Dr. Tom Heaps Consultant Acute Physician

CASE 14: RECURRENT VTE3. Will confirmation of recurrent DVT or PE change my

management? may influence duration of anticoagulation if first episode diagnosis of PE in patient being treated for DVT may affect risk

stratification and follow-up (ECHO) if recurrent distinct episodes of VTE despite optimal anticoagulation

options; switching to long-term LMWH higher target INR e.g. 3.0-3.5 (increased bleeding risk) IVC filter (risk of complications, will not prevent DVT)

4. Am I missing thrombophilia, occult malignancy or something else? patient underwent CTV to r/o malignancy/venous obstruction compression of left iliac vein by right internal iliac artery (May-

Thurner syndrome); stented

Page 56: A MASTERCLASS IN: VENOUS THROMBOEMBOLISM (VTE) Dr. Tom Heaps Consultant Acute Physician

VTE: KEY LEARNING POINTS

Low threshold of suspicion for PE – cannot rely on clinical features alone

Assess clinical pre-test probability in ALL patients before taking d-dimer

Thinking should not stop once diagnosis made – why, what, how?

Ix for cancer and consider long-term/indefinite anticoagulation after single episode of idiopathic/unprovoked VTE

Thrombophilia testing rarely indicated

Consider CDT in younger patients with massive proximal DVT

Limitations of novel anticoagulants

Special cases – pregnancy, UEDVT, IVDU, malignancy, isolated pelvic DVT, thrombophlebitis, recurrent VTE

Follow-up patients for long-term complications – PTS, pHTN

Page 57: A MASTERCLASS IN: VENOUS THROMBOEMBOLISM (VTE) Dr. Tom Heaps Consultant Acute Physician

ANY OTHER QUESTIONS?